Regulation of the expression of the Cl-/anion exchanger pendrin in mouse kidney by acid-base status.
BACKGROUND: Pendrin belongs to a superfamily of Cl-/anion exchangers and is expressed in the inner ear, the thyroid gland, and the kidney. In humans, mutations in pendrin cause Pendred syndrome characterized by sensorineural deafness and goiter. Recently pendrin has been localized to the apical side of non-type A intercalated cells of the cortical collecting duct, and reduced bicarbonate secretion was demonstrated in a pendrin knockout mouse model. To investigate a possible role of pendrin in modulating acid-base transport in the cortical collecting duct, we examined the regulation of expression of pendrin by acid-base status in mouse kidney. METHODS: Mice were treated orally either with an acid or bicarbonate load (0.28 mol/L NH4Cl or NaHCO3) or received a K+-deficient diet for one week. Immunohistochemistry and Western blotting was performed. RESULTS: Acid-loading caused a reduction in pendrin protein expression levels within one day and decreased expression to 23% of control levels after one week. Concomitantly, pendrin protein was shifted from the apical membrane to the cytosol, and the relative abundance of pendrin positive cells declined. Similarly, in chronic K+-depletion, known to elicit a metabolic alkalosis, pendrin protein levels decreased and pendrin expression was shifted to an intracellular pool with the relative number of pendrin positive cells reduced. In contrast, following oral bicarbonate loading pendrin was found exclusively in the apical membrane and the relative number of pendrin positive cells increased. CONCLUSIONS: These results are in agreement with a potential role of pendrin in bicarbonate secretion and regulation of acid-base transport in the cortical collecting duct.
Wagner, CA; Finberg, KE; Stehberger, PA; Lifton, RP; Giebisch, GH; Aronson, PS; Geibel, JP
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